2. Academic Validation
  3. RASSF1A inhibits gastric cancer metastasis by reducing neutrophil infiltration and neutrophil extracellular trap formation via ribosome biogenesis

RASSF1A inhibits gastric cancer metastasis by reducing neutrophil infiltration and neutrophil extracellular trap formation via ribosome biogenesis

  • Int Immunopharmacol. 2026 May 1:176:116475. doi: 10.1016/j.intimp.2026.116475.
Yu Chen 1,  Lingchen Dai 1,  Guohao Chen 1,  Shukang Deng 1,  Ruiqing Liu 1,  Wanjiang Xue 2,  Yilin Hu 3,  Jianfeng Yi 4
Affiliations

Affiliations

  • 1 Department of Gastrointestinal Surgery, Affiliated Hospital of Nantong University, Medical School of Nantong University, Nantong 226001, Jiangsu, China; Research Center of Clinical Medicine, Affiliated Hospital of Nantong University, Nantong 226001, Jiangsu, China.
  • 2 Department of Gastrointestinal Surgery, Affiliated Hospital of Nantong University, Medical School of Nantong University, Nantong 226001, Jiangsu, China; Research Center of Clinical Medicine, Affiliated Hospital of Nantong University, Nantong 226001, Jiangsu, China; Nantong Key Laboratory of Gastrointestinal Oncology, Nantong 226001, Jiangsu, China.
  • 3 Department of Gastrointestinal Surgery, Affiliated Hospital of Nantong University, Medical School of Nantong University, Nantong 226001, Jiangsu, China; Research Center of Clinical Medicine, Affiliated Hospital of Nantong University, Nantong 226001, Jiangsu, China; Nantong Key Laboratory of Gastrointestinal Oncology, Nantong 226001, Jiangsu, China. Electronic address: [email protected].
  • 4 Department of Gastrointestinal Surgery, Affiliated Hospital of Nantong University, Medical School of Nantong University, Nantong 226001, Jiangsu, China. Electronic address: [email protected].
PMID: 41833106 DOI: 10.1016/j.intimp.2026.116475
Abstract

RASSF1A is a well-established tumor suppressor implicated in various human malignancies; however, its specific role in the metastasis of gastric Cancer (GC) remains poorly understood. In this study, we observed that RASSF1A expression is frequently silenced in GC tissues compared to adjacent normal tissues, with its loss significantly correlating with metastatic progression. Immunohistochemical analysis further revealed a negative correlation between RASSF1A levels and the infiltration of neutrophils, as well as the formation of neutrophil extracellular traps (NETs). Mechanistically, knockdown of RASSF1A triggers the JNK-JUN signaling pathway, which subsequently accelerates ribosome biogenesis. This metabolic shift enhances the translation of pro-inflammatory chemokines, thereby promoting neutrophil recruitment and NETs formation. Furthermore, our findings demonstrate that RASSF1A interacts with LTBR, effectively inhibiting the LIGHT-induced recruitment of TRAF2 and suppressing downstream JNK-JUN activation. Collectively, our results suggest that RASSF1A functions as a critical inhibitor of GC metastasis by modulating the chemokine-neutrophil axis, offering novel insights into its role as a therapeutic target in GC.

Keywords

Gastric cancer; Metastasis; NETs; Neutrophil; RASSF1A.

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